The effect of NLRP3 on airway epithelial-mesenchymal transition by regulating Th17/Treg imbalance in asthmatic mice
10.13431/j.cnki.immunol.j.20240057
- VernacularTitle:NLRP3调节Th17/Treg失衡对哮喘小鼠气道上皮间质转化的影响
- Author:
Beibei CHENG
1
,
2
;
Guoran PENG
;
Lingling ZHOU
;
Feiying WANG
;
Silin XIE
;
Jian YI
;
Aiguo DAI
Author Information
1. 410208 长沙,湖南中医药大学医学院呼吸疾病研究室
2. 410208 长沙,湖南中医药大学血管生物学与转化医学湖南省重点实验室
- Keywords:
Asthma;
Epithelial-mesenchymal transition;
NLRP3;
Th17;
Treg cell
- From:
Immunological Journal
2024;40(5):440-445
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to explore the correlation between alterations in NLRP3 levels and Th17/Treg imbalance in asthmatic mice undergoing epithelial-mesenchymal transition(EMT).A murine model of asthma was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).Mice were randomly grouped into asthma model group and normal control group.The airway reactivity was detected with non-invasive lung function instrument.Hematoxylin and Eosin(HE)and Masson's trichrome staining were applied to evaluate the histopathological injury of lung tissue and the extent of lung fibrosis;RT-qPCR was applied to detect EMT-related biomarkers(Snail,E-Cadherin,N-Cadherin),the specific transcription factors of T cell subsets(RoRγt,Foxp3)and NLRP3 in lung tissue of mice;Western blot was used to detect the protein expression of E-cadherin,N-Cadherin and NLRP3 in lung tissue of mice.The Th17 and Treg cell populations in the spleen were enumerated via flow cytometry.Furthermore,the expression levels of NLRP3,IL-17 and IL-10 in bronchoalveolar lavage fluid(BALF)were analyzed by Giemsa staining.Compared with the control group,the asthma model group showed higher level of airway resistance,coupled with an obviously decrease in pulmonary ventilation compliance.Pathological alterations in lung tissue were evident,characterized by thickening of the airway epithelium,airway stenosis,infiltration of inflammatory cells,higher expression levels of N-Cadherin and NLRP3 proteins(P<0.05),lower expression level of E-Cadherin(P<0.001)and higher levels of marker genes(Snail and N-Cadherin)in lung tissue.Furthermore,model mice demonstrated higher level of NLRP3 in BALF(P<0.05),higher level of Th17 in spleen,and higher levels of retinoic acid orphan receptor(ROR)-γt mRNA(P<0.05)and Th17-related cytokines(IL-17)(P<0.01).Concurrently,model mice also showed an obviously decrease in the prevalence of Treg cells,Forkhead box Foxp3 mRNA(P<0.001),and Treg-related cytokine IL-10(P<0.05).The results of the Pearson correlation analysis indicated that the level of NLRP3 mRNA was positively correlated the ratio of RoR γt mRNA,but negatively correlated with Foxp3 mRNA in the lung tissue of asthmatic mice.Additionally,NLRP3 in BALF demonstrated a positive correlation with IL-17 and a negative correlation with IL-10.In conclusion,These findings suggest that NLRP3 may trigger bronchial EMT by exacerbating the immune imbalance of Th17/Treg cells.
